4. Cancer Prevention Vaccine (continuation from previous comments 7995)
4. HSV-2_Herpes simplex virus type 2 (cofactor to HIV and certain types of brain cancer)
Disease burden. HSV-2 prevalence is increasing worldwide. There is now ample evidence that Herpes simplex virus type 2 (HSV-2) infection, the most common cause of genital ulcers worldwide, is a major cofactor favoring HIV infection. HSV-2 prevalence is generally higher in developing than in developed countries and in urban than rural areas. The HSV-2 prevalence in developing countries, although very high, varies widely according to the countries, the gender, urban versus rural areas, ranging from 2-74%.
Vaccines. Herpesvirus 2 belongs to the enveloped Herpesviridae family. The first generation of vaccines was recombinant subunit viral glycoproteins. Chiron developed a two-component (30 mg of both gB2 and gD2 glycoproteins) subunit vaccine formulated in MF59 adjuvant and SmithKline Beecham a monovalent vaccine (gD2) formulated in alum + monophosphoryl lipid A (Corixa). The Chiron vaccine induced very high antibody titres, and efficacy in women for the first 5 months was 26%, but this protection against infection was not sustained. Chiron doesn't have an active HSV-2 vaccine at present. The Phase III trials of the vaccine developed by GlaxoSmithKline (glycoprotein gD2 formulated with adjuvant) showed limited efficacy, depending on gender and previous exposure to HSV-1. Indeed, these trials showed a 73% and 74% efficacy (P=0.01 and 0.02, respectively) against genital herpes disease in HSV-1- and HSV-2-negative women. Trends towards protection in women against HSV infection were also seen in both studies (39-48% efficacy), although not statistically significant. The main disadvantages of this vaccine are the apparent failure to improve on protection provided by HSV-1 infection and the need for frequent administration to boost host immunity. Further efficacy trials of this vaccine, which has already been administrated in about 7 500 individuals, are pending in collaboration with NIAID . A novel HSV-2 candidate vaccine has been developed by Cantab Pharmaceuticals (now Xenova )/GlaxoSmithKline based on a genetically Disabled Infectious Single Cycle (DISC, glycoprotein H-deleted, ICP8 gene mutation) replicative vaccine, which is believed could have higher efficacy than previous vaccines. This new candidate vaccine has been tested in Phase II trials in the US and UK, showing good tolerance and inducing neutralizing antibodies and CTL in 83% of the vaccine recipients. Nevertheless, no difference in time to recurrence was observed in this therapeutic candidate vaccine in HSV-2 seropositive symptomatic, and no difference was recorded in shedding. Therefore, Xenova (without GSK) is refocusing their programme on prophylactic applications for their DISC vaccine. One complexity of evaluating protection against infection induced by the DISC vaccine is that, because of the similarity of the disabled virus and wild HSV-2, it will not be possible to distinguish natural infection from vaccine-induced immunity. Another live, replication-impaired vaccine is currently under development by Avant Immunotherapeutics . AuRx, Inc concentrate on live genetically-attenuated replication-competent vaccines and PowderJect and Merck on DNA vaccine formulations.
A vaccine which protects only women would be expected to reduce HSV infection and disease in vaccinated women, decrease the rate of neonatal HSV infection, have an impact on the epidemic spread of genital herpes in men and women, and finally possibly reduce acquisition and transmission of HIV infection. Failure to protect HSV-1 seropositive women may result if vaccination does not add to the natural protection provided by HSV-1. In this case administration of vaccine to young children, before HSV1 occurs, would not be particularly helpful. Lack of efficacy of vaccines in HSV1-infected individuals would render the vaccine useless in develo